Abstract 12623: Vascular Regenerative Capacity: A Window into the Pathobiology of Obesity Paradox

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Anurag Mehta ◽  
Qi Meng ◽  
Shivang Desai ◽  
Melroy D'Souza ◽  
Annie Ho ◽  
...  
Keyword(s):  
Obesity Paradox ◽  
Cardiovascular Death ◽  
Obese Patients ◽  
Linear Regression Models ◽  
Regenerative Capacity ◽  
Cox Models ◽  
Android Fat ◽  
Asymptomatic Individuals ◽  
Similar Risk

Introduction: Obese patients (BMI≥30 kg/m 2 ) with CAD have better outcomes as compared with non-obese patients, but the underlying pathobiology is unclear. Hypothesis: Obesity is directly associated with vascular regenerative capacity, measured as circulating progenitor cell (CPC) count, and this association provides insight into obesity paradox pathobiology. Methods: CPCs were enumerated by flow cytometry as CD45 med+ cells expressing CD34+, CD133+, and CXCR4+ epitopes in 672 asymptomatic individuals (50 y, 66% women, 23% Black, 28% obese) and 1,277 patients with CAD (66 y, 39% women, 22% Black, 39% obese). Association of obesity with CPC counts was analyzed using multivariable-adjusted linear regression models. Association of obesity and CPCs with cardiovascular death/myocardial infarction events over 3.5-y follow-up was studied using Kaplan-Meir survival curves and Cox models. Results: Obesity was independently associated with 16-34% higher CPC count (CD34+, CD34+/CD133+, and CD34+/CXCR4+) in asymptomatic individuals. This association was not attenuated after adjusting for measures of systemic inflammation, insulin resistance, or insulin secretion. Cardiorespiratory fitness and android fat only partly attenuated the obesity-CPC relationship. In patients with CAD, obesity was independently associated with 8-12% higher CPC counts, and with 30% lower outcome risk. Lower CPC counts were associated with outcome risk in obese patients. Obese patients with high CD34+ count (≥median) were at a lower risk, while obese participants with low counts (<median) were at a similar risk as compared with non-obese patients with high counts. The highest risk was observed in non-obese patients with low counts. Similar results were observed with CD34+/CD133+ and CD34+/CXCR4+ cells. Conclusions: Obesity is directly associated with vascular regenerative capacity, and the obesity paradox in CAD is observed in obese patients with high, but not low, CPC counts.

scholarly journals Vascular Regenerative Capacity and the Obesity Paradox in Coronary Artery Disease

2021 ◽  
Author(s):  
Anurag Mehta ◽  
Qi Meng ◽  
Xiaona Li ◽  
Shivang R. Desai ◽  
Melroy S. D’Souza ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Lower Risk ◽  
Obesity Paradox ◽  
Hazard Ratio ◽  
Adverse Outcomes ◽  
Linear Regression Models ◽  
Regenerative Capacity ◽  
Artery Disease ◽  
Asymptomatic Individuals

Objective: The underlying pathobiology of the paradoxical relationship between obesity and outcomes in coronary artery disease (CAD) is unclear. Our objective was to determine the association between obesity and circulating progenitor cell (CPC) counts—a measure of intrinsic regenerative capacity—in asymptomatic individuals and patients with CAD and its impact on the obesity paradox. Approach and Results: CPCs were enumerated by flow cytometry as CD45 med+ cells expressing CD34+, CD133+, and CXCR4+ epitopes in 672 asymptomatic individuals (50 years of age; 28% obese) and 1277 CAD patients (66 years of age; 39% obese). The association between obesity and CPCs was analyzed using linear regression models. The association between obesity and CPCs with cardiovascular death/myocardial infarction events over 3.5-year follow-up in CAD was studied using Cox models. Obesity was independently associated with 16% to 34% higher CPC counts (CD34+, CD34+/CD133+, and CD34+/CXCR4+) in asymptomatic individuals. This association was not attenuated by systemic inflammation, insulin resistance, or secretion but partly attenuated by cardiorespiratory fitness and body composition. In patients with CAD, obesity was associated with 8% to 12% higher CPC counts and 30% lower risk of adverse outcomes. Compared with nonobese patients, only obese patients with high CPC counts (CD34+ cells ≥median, 1806 cells/mL) were at a lower risk (hazard ratio, 0.52 [95% CI, 0.31–0.88]), whereas those with low counts (<median) were at a similar risk (hazard ratio, 0.75 [95% CI, 0.48–1.15]). Conclusions: Obesity is associated with higher CPC counts. The obesity paradox of improved outcomes with obesity in CAD is limited to patients with intact regenerative capacity who have CPC counts.

scholarly journals Revisiting the obesity paradox in heart failure: Per cent body fat as predictor of biomarkers and outcome

2019 ◽  
Vol 26 (16) ◽  
pp. 1751-1759 ◽  
Author(s):  
Alberto Aimo ◽  
James L Januzzi ◽  
Giuseppe Vergaro ◽  
Aldo Clerico ◽  
Roberto Latini ◽  
...  
Keyword(s):  
Heart Failure ◽  
Body Fat ◽  
Troponin T ◽  
High Sensitivity ◽  
Obesity Paradox ◽  
Cardiovascular Death ◽  
Obese Patients ◽  
Jackson Pollock ◽  
Reduced Ejection Fraction ◽  
Patient Prognosis

Aims Obesity defined by body mass index (BMI) is characterized by better prognosis and lower plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) in heart failure. We assessed whether another anthropometric measure, per cent body fat (PBF), reveals different associations with outcome and heart failure biomarkers (NT-proBNP, high-sensitivity troponin T (hs-TnT), soluble suppression of tumorigenesis-2 (sST2)). Methods In an individual patient dataset, BMI was calculated as weight (kg)/height (m) 2 , and PBF through the Jackson–Pollock and Gallagher equations. Results Out of 6468 patients (median 68 years, 78% men, 76% ischaemic heart failure, 90% reduced ejection fraction), 24% died over 2.2 years (1.5–2.9), 17% from cardiovascular death. Median PBF was 26.9% (22.4–33.0%) with the Jackson–Pollock equation, and 28.0% (23.8–33.5%) with the Gallagher equation, with an extremely strong correlation ( r = 0.996, p < 0.001). Patients in the first PBF tertile had the worst prognosis, while patients in the second and third tertile had similar survival. The risks of all-cause and cardiovascular death decreased by up to 36% and 27%, respectively, per each doubling of PBF. Furthermore, prognosis was better in the second or third PBF tertiles than in the first tertile regardless of model variables. Both BMI and PBF were inverse predictors of NT-proBNP, but not hs-TnT. In obese patients (BMI ≥ 30 kg/m2, third PBF tertile), hs-TnT and sST2, but not NT-proBNP, independently predicted outcome. Conclusion In parallel with increasing BMI or PBF there is an improvement in patient prognosis and a decrease in NT-proBNP, but not hs-TnT or sST2. hs-TnT or sST2 are stronger predictors of outcome than NT-proBNP among obese patients.

Abstract 5010: Determining the Plasticity of Cardiovascular Risk in the Elderly: A role for serial NT-proBNP measurement

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Christopher Defilippi ◽  
Robert Christenson ◽  
John Gottdiener ◽  
Willem J Kop ◽  
Stephen L Seliger
Keyword(s):  
Risk Factors ◽  
Cardiovascular Health ◽  
The Elderly ◽  
Cardiovascular Death ◽  
Health Study ◽  
Cardiovascular Health Study ◽  
Continuous Measure ◽  
Cox Models ◽  
Low Levels

In the elderly, with decades of exposure to cardiovascular (CV) risk factors, CV prognosis is often considered static. We hypothesized that CV risk is dynamic reflected by changes in NTproBNP over time. We measured NTproBNP at baseline and after 2–3 years in the Cardiovascular Health Study. Long-term risk of CV death according to change in NTproBNP was estimated with the Kaplan-Meier method. We used Cox models to test if effect of change in NTproBNP was independent of demographic and CV risk factors, baseline NTproBNP, renal function, coronary disease, and CV medications. Participants were categorized at baseline as < (low) or >=190pg/mL (high) levels, based on an observed increase in risk above this level. A significant change in NTproBNP category was defined as a change of >25% to a level above or below this cut-point, based on the reported biological variability of NTproBNP. Change in NTproBNP was also evaluated as a continuous measure. Serial NTproBNP levels were measured in 2,975 (86%) of 3,469 participants (age 75±5 years) without heart failure and who had a follow-up visit. CV death was different between those with low levels that remained low (n=1,774) vs. those with low levels that became high (n=468) (1.1 vs. 2.7 per 100 person-yrs, p<.001) and those with high levels that remained high (n=621) vs. those with high levels that became low (n=112) (4.2 vs. 1.6 per 100 person-yrs, p<.001) (figure ). As a continuous measure, change in NTproBNP was linearly associated with CV mortality risk after adjustment (per Ln-fold increment: RR=1.47, p<.001). Dynamic changes in NTproBNP levels reflect dramatic change in CV prognosis in the elderly. Proportion without Cardiovascular death, by initial and follow-up NT-proBNP

scholarly journals Impact of sex and myocardial function on association of obesity with mortality in Asian patients with acute heart failure: a retrospective analysis from the STRATS-AHF registry

BMJ Open ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. e031608 ◽  
Author(s):  
Chan Soon Park ◽  
Jun-Bean Park ◽  
Jin Joo Park ◽  
Jae-Hyeong Park ◽  
Goo-Yeong Cho
Keyword(s):  
Heart Failure ◽  
Health Status ◽  
Significant Interaction ◽  
Myocardial Function ◽  
Obesity Paradox ◽  
Metabolic Health ◽  
Obese Patients ◽  
Link Type ◽  
Protective Association

ObjectivesImpact of sex and myocardial function on the obesity paradox in heart failure (HF) is unknown. We explored whether sex, myocardial function, and left ventricular (LV) geometry explains the protective association of body mass index (BMI) with mortality, and investigated whether metabolic health status affects this association.DesignA multicentre cohort study with patients with acute HF admitted from January 2009 to December 2016 with a median follow-up of 33.7 months.SettingThree tertiary hospitals.ParticipantsA total of 2021 overweight-to-obese (OW) and 1543 normal-weight (NW) patients with acute HF.MeasurementsThe primary outcome was all-cause mortality. Patients were categorised as either OW (BMI≥23kg/m2) or NW (BMI<23kg/m2). BMI was used as both categorical and continuous variables. Clinical, laboratory and echocardiographic measures, including LV global longitudinal strain (LV-GLS), LV-ejection fraction, LV geometry, were obtained.ResultsDuring the follow-up period, 1392 patients died (685 OW and 707 NW). BMI was significantly associated with mortality in univariate (HR=0.929 per kg/m2, p<0.001) and multivariate analyses (HR=0.954 per kg/m2, p<0.001). In multivariable fractional polynomials, higher BMIs were associated with lower mortality overall and in subgroups by sex, LV-GLS and LV geometry, with a steeper association in men (p-interaction <0.001). In women, there were significant interactions of BMI with LV-GLS (p-interaction=0.044) and age (p-interaction=0.040) for mortality; the protective association of BMI with mortality was confined to subgroups with high LV-GLS (>10.1%) or elderly patients (≥75 years). In men, this association was found in all subgroups without significant interaction. Metabolically healthy obese patients had better survival than metabolically unhealthy obese patients (log-rank p<0.001).ConclusionsIn women, a significant interaction was observed between BMI and age or LV-GLS in association with mortality, suggesting that sex, ageing and myocardial dysfunction can affect the magnitude of the obesity paradox in HF. Metabolic health status provides prognostic information beyond obesity status.Trial registration numberRegistry: ClinicalTrials.gov Number:NCT03513653(https://clinicaltrials.gov/ct2/show/NCT03513653)

scholarly journals Combined association of key risk factors on ischaemic outcomes and bleeding in patients with myocardial infarction

Heart ◽  
2019 ◽  
pp. heartjnl-2018-314590 ◽  
Author(s):  
Daniel Lindholm ◽  
Giovanna Sarno ◽  
David Erlinge ◽  
Bodil Svennblad ◽  
Lars Pål Hasvold ◽  
...  
Keyword(s):  
Risk Factors ◽  
Myocardial Infarction ◽  
Risk Factor ◽  
Major Bleeding ◽  
Unmet Need ◽  
Cardiovascular Death ◽  
Cox Models ◽  
Multiple Risk Factors ◽  
Evidence Based Care

ObjectiveIn patients with myocardial infarction (MI), risk factors for bleeding and ischaemic events tend to overlap, but the combined effects of these factors have scarcely been studied in contemporary real-world settings. We aimed to assess the combined associations of established risk factors using nationwide registries.MethodsUsing the Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies registry, patients with invasively managed MI in 2006–2014 were included. Six factors were assessed in relation to cardiovascular death (CVD)/MI/stroke, and major bleeding: age ≥65, chronic kidney disease, diabetes, multivessel disease, prior bleeding and prior MI.ResultsWe studied 100 879 patients, of whom 20 831 (20.6%) experienced CVD/MI/stroke and 5939 (5.9%) major bleeding, during 3.6 years median follow-up. In adjusted Cox models, all factors were associated with CVD/MI/stroke, and all but prior MI were associated with major bleeding. The majority (53.5%) had ≥2 risk factors. With each added risk factor, there was a marked but gradual increase in incidence of the CVD/MI/stroke. This was seen also for major bleeding, but to a lesser extent, largely driven by prior bleeding as the strongest risk factor.ConclusionsThe majority of patients with MI had two or more established risk factors. Increasing number of risk factors was associated with higher rate of ischaemic events. When excluding patients with prior major bleeding, bleeding incidence rate increased only minimally with increasing number of risk factors. The high ischaemic risk in those with multiple risk factors highlights an unmet need for additional preventive measures.

scholarly journals Obesity and Chronic Obstructive Pulmonary Disease: Is Fatter Really Better?

2014 ◽  
Vol 21 (5) ◽  
pp. 297-301 ◽  
Author(s):  
Roxana G Galesanu ◽  
Sarah Bernard ◽  
Karine Marquis ◽  
Yves Lacasse ◽  
Paul Poirier ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Chronically Ill ◽  
Obesity Paradox ◽  
Work Rate ◽  
Chronic Obstructive ◽  
Obese Patients ◽  
Obstructive Pulmonary Disease ◽  
Arterial Blood

BACKGROUND: Overweight/obesity is associated with longer survival in chronically ill patients, a phenomenon referred to as the ‘obesity paradox’.OBJECTIVE: To investigate whether the obesity paradox in patients with chronic obstructive pulmonary disease (COPD) is due to fat accumulation or confounding factors.METHODS: A total of 190 patients with stable COPD who underwent a mean (± SD) follow-up period of 72±34 months were enrolled. Anthropometry, pulmonary function tests, midthigh muscle cross-sectional area obtained using computed tomography (MTCSACT), arterial blood gas and exercise testing data were measured at baseline. Patients were categorized into two subgroups according to body mass index (BMI) <25 kg/m2or ≥25 kg/m2(normal and overweight/obese, respectively).RESULTS: Seventy-two patients (38%) died during the follow-up period. Survival tended to be better in the overweight/obese patients but this difference did not reach statistical significance. Overweight/obese patients had better lung function and a larger MTCSACTthan those with normal BMI (P<0.001). Overweight/obese patients also had a significantly higher peak work rate than patients with normal BMI (P<0.001).PaO2andPaCO2were not significantly different in the two groups. When adjusted forPaCO2, peak work rate and MTCSACT, the tendency for improved survival in overweight/obese patients disappeared. In fact, when these variables were considered in the survival analysis, patients with lower BMI tended to have better survival.CONCLUSION: These results suggest that important confounders, such as hypercapnia, exercise capacity and muscle mass, should be considered when interpreting the association between increased BMI and survival in patients with COPD.

Abstract MP27: Weight Change, BMI, and Mortality Among Survivors of Myocardial Infarction: Analysis of Two Prospective US Cohort Studies

Circulation ◽  
2018 ◽  
Vol 137 (suppl_1) ◽  
Author(s):  
Laila Al-Shaar ◽  
Yanping Li ◽  
Eric Rimm ◽  
JoAnn E Manson ◽  
Frank Hu ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Weight Change ◽  
Normal Weight ◽  
Health Study ◽  
Obese Patients ◽  
Cox Models ◽  
Hazard Ratios ◽  
Before And After ◽  
Cvd Mortality

Background: The relation between BMI, weight change and mortality among survivors of Myocardial Infarction (MI) remains controversial, with some studies reporting favorable survival outcomes among overweight and obese patients, as compared to those with normal weight. We aim to examine the relationship between BMI reported shortly before and after MI diagnosis in addition to weight change with all-cause and cardiovascular disease (CVD) mortality among MI survivors. Methods: Using the data from Nurses’ Health Study (NHS) and Health Professionals Follow up Study (HPFS) cohorts, we studied 4278 participants who were free of CVD and cancer before their MI. Weight change (in BMI units) was categorized as loss of (> 4, 2-4, <2-0 (reference)), or gain of (0.1-2, or >2) units. Multivariable Cox models were used to estimate hazard ratios and 95 % confidence interval for mortality across BMI/weight change categories. Results: During up to 36 (NHS) and 28 (HPFS) years of follow-up post-MI, there were 2071 all-cause and 835 CVD deaths. Overweight patients with BMI before or after MI of 25-27.49 kg/m 2 had decreased mortality as compared to normal weight patients (22.5-24.9 kg/m 2 ). All-cause mortality increased progressively with higher BMI. Obese patients (BMI≥30) had the highest risk of CVD mortality (HR=1.35; 95% CI, 1.06-1.73). Among MI patients who had never smoked (N=1484) or were younger than 65 years of age at the time of diagnosis (N=1873), no survival advantage was observed for overweight/obese patients. Compared to stable weight (a BMI reduction of 0-1.99 units) from before to after MI, a reduction of 2-4 or >4 BMI units was associated with increased mortality (HR=1.12; 95% CI, 0.96-1.29 and 1.42; 95% CI, 1.17-1.71 respectively, Figure). Conclusions: We observed a J-shaped association between BMI and mortality among all MI patients, but not among those who had never smoked or were younger than 65 years of age. Weight loss associated with acute MI, potentially related to disease severity, is an important predictor of higher mortality.

scholarly journals No Obesity Paradox—BMI Incapable of Adequately Capturing the Relation of Obesity with All-Cause Mortality: An Inception Diabetes Cohort Study

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Mohammadreza Bozorgmanesh ◽  
Banafsheh Arshi ◽  
Farhad Sheikholeslami ◽  
Fereidoun Azizi ◽  
Farzad Hadaegh
Keyword(s):  
Obesity Paradox ◽  
Diabetic Patients ◽  
Hip Circumference ◽  
Community Based ◽  
Confounding Effect ◽  
Anthropometric Measures ◽  
Cox Models ◽  
All Cause Mortality ◽  
Adjusted Model

Background. To reconcile “the obesity paradox,” we tested if (1) the contribution of anthropometric measures to mortality was nonlinear and (2) the confounding of hip circumference contributed to the obesity paradox recently observed among diabetic patients.Methods. We analyzed data of diabetic patients attending a community-based prospective, “Tehran lipid and glucose study.” In the mortality analysis, anthropometric measures—body mass index (BMI), waist, and hip circumference—were assessed using Cox models incorporating cubic spline functions.Results. During 12 990 person-years follow-up, BMI levels below 27 and those above 40 kg·m−2were associated with increased mortality. When we added waist circumference to the BMI in the multivariate-adjusted model, the steepness of BMI-mortality association curve slope for values below 27 kg·m−2increased, whereas the steepness of BMI-mortality association curve slope for values above this threshold decreased. Further adjusting the model for hip circumference, the steepness of the slopes of the association curve moved towards null on both extremes and no associations between BMI and all-cause mortality remained.Conclusion. BMI harbors intermixed positive and negative confounding effects on mortality of waist and hip circumference. Failing to control for the confounding effect of hip circumference may stymie unbiased hazard estimation and render conclusions paradoxical.

P4542Revisiting the obesity paradox in heart failure: percent body fat as predictor of biomarkers and outcome

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
A Aimo ◽  
J Januzzi ◽  
G Vergaro ◽  
R Latini ◽  
I S Anand ◽  
...  
Keyword(s):  
Heart Failure ◽  
Body Fat ◽  
Troponin T ◽  
High Sensitivity ◽  
Obesity Paradox ◽  
Cardiovascular Death ◽  
Percent Body Fat ◽  
Obese Patients ◽  
Jackson Pollock ◽  
Patient Prognosis

Abstract Background Obesity defined by body mass index (BMI) is characterized by better prognosis and lower plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) in heart failure (HF). We assessed whether another anthropometric measure, percent body fat (PBF), reveals different associations with outcome and HF biomarkers (NT-proBNP, high-sensitivity troponin T [hs-TnT], soluble suppression of tumorigenesis-2 [sST2]). Methods In an individual patient dataset, BMI was calculated as weight (kg)/height (m)2, and PBF through the Jackson-Pollock and Gallagher equations. Results Out of 6468 patients (median 68 years, 78% men, 76% ischaemic HF, 90% reduced EF), 24% died over 2.2 years (1.5–2.9), 17% from cardiovascular death. Median PBF was 26.9% (22.4–33.0%) with the Jackson-Pollock equation, and 28.0% (23.8–33.5%) with the Gallagher equation, with an extremely strong correlation (r=0.996, p<0.001). Patients in the first PBF tertile had the worst prognosis, while patients in the second and third tertile had similar survival. The risks of all-cause and cardiovascular death decreased by up to 36% and 27%, respectively, per each doubling of PBF. Furthermore, prognosis was better in the second or third PBF tertiles than in the first tertile regardless of model variables. Both BMI and PBF were inverse predictors of NT-proBNP, but not hs-TnT. In obese patients (BMI ≥30 kg/m2, third PBF tertile), hs-TnT and sST2, but not NT-proBNP, independently predicted outcome. Conclusion Patient prognosis improves with either BMI or PBF. Obesity, assessed with BMI or PBF, is associated with lower NT-proBNP but not hs-TnT or sST2. hs-TnT or sST2 are stronger prognostic predictors than NT-proBNP among obese patients.

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